crossing96/oncoscreening huggingface dataset:
Radiation therapy before radical cystectomy combined with immunotherapy in locally advanced bladder cancer - study protocol of a prospective, single arm, multicenter phase II trial (RACE IT).	"BACKGROUND: Patients with locally advanced bladder cancer (cT3/4 cN0/N+ cM0) have a poor prognosis despite radical surgical therapy and perioperative chemotherapy. Preliminary data suggest that the combination of radiation and immunotherapy does not lead to excess toxicity and may have synergistic (abscopal) anti-tumor effects. We hypothesize that the combined preoperative application of the PD-1 checkpoint-inhibitor Nivolumab with concomitant radiation therapy of the bladder and pelvic region followed by radical cystectomy with standardized lymphadenectomy is safe and feasible and might improve outcome for patients with locally advanced bladder cancer. METHODS: Study design: ""RACE IT"" (AUO AB 65/18) is an investigator initiated, prospective, multicenter, open, single arm phase II trial sponsored by Technical University Munich. Study drug and funding are provided by the company Bristol-Myers Squibb. Study treatment: Patients will receive Nivolumab 240 mg i.v. every 2 weeks for 4 cycles preoperatively with concomitant radiation therapy of bladder and pelvic region (max. 50.4 Gy). Radical cystectomy with standardized bilateral pelvic lymphadenectomy will be performed between week 11-15. Primary endpoint: Rate of patients with completed treatment consisting of radio-immunotherapy and radical cystectomy at the end of week 15. Secondary endpoints: Acute and late toxicity, therapy response and survival (1 year follow up). Main inclusion criteria: Patients with histologically confirmed, locally advanced bladder cancer (cT3/4, cN0/N+), who are ineligible for neoadjuvant, cisplatin-based chemotherapy or who refuse neoadjuvant chemotherapy. Main exclusion criteria: Patients with metastatic disease (lymph node metastasis outside pelvis or distant metastasis) or previous chemo-, immune- or radiation therapy. Planned sample size: 33 patients, interim analysis after 11 patients. DISCUSSION: This trial aims to evaluate the safety and feasibility of the combined approach of preoperative PD-1 checkpoint-inhibitor therapy with concomitant radiation of bladder and pelvic region followed by radical cystectomy. The secondary objectives of therapy response and survival are thought to provide preliminary data for further clinical evaluation after successful completion of this trial. Recruitment has started in February 2019. TRIAL REGISTRATION: Protocol Code RACE IT: AB 65/18; EudraCT: 2018-001823-38; Clinicaltrials.gov: NCT03529890; Date of registration: 27 June 2018."	bladder
Predictive value of cadherin-11 for subsequent recurrence and progression in non-muscle invasive bladder cancer.	BACKGROUND: Cadherin-11 (CDH11) is a type II cadherin and reported to function as an oncogene in various cancers. Our present study aims to investigate the role of CDH11 in bladder cancer (BCA). METHODS: Bioinformatics analysis was performed in four independent microarray data including 56 non-muscle-invasive bladder cancer (NMIBC) and 132 muscle-invasive bladder cancer (MIBC) tissues from Gene Expression Omnibus to screen out differentially expressed genes. Next, we detected CDH11 expression in BCA specimens and cell lines by qPCR and western blotting assays. Immunohistochemical analyses were performed in 209 paraffin-embedded BCA samples and 30 adjacent normal bladder tissues. RESULTS: Bioinformatics analysis revealed that CDH11 had a higher expression level in MIBC tissues than in NMIBC, which was consistent with our clinical BCA specimens and cell lines at both mRNA and protein levels. Immunohistochemical analysis demonstrated that over-expression of CDH11 was closely related to the histological grade, pT status, tumour size and poor outcomes of BCA patients. What's more, CDH11 (area under curve (AUC) = 0.673 and 0.735) had a better predictive value than E-cadherin (AUC = 0.629 and 0.629) and a similar discrimination with the European Organization for Research and Treatment of Cancer (EORTC) score system (AUC = 0.719 and 0.667) in evaluating potential recurrence and progression of NMIBC. Moreover, combination of CDH11 and EORTC score system was the best predictive model in predicting recurrence of NMIBC (AUC = 0.779) among the three models. CONCLUSIONS: CDH11 was a reliable therapeutic target in BCA and a useful index to predict the possibilities of recurrence and progression in NMIBC patients.	bladder
LncARSR sponges miR-129-5p to promote proliferation and metastasis of bladder cancer cells through increasing SOX4 expression.	Emerging evidences have indicated that long non-coding RNAs (lncRNAs) are potential biomarkers, playing important roles in the development of cancer. LncRNA Activated in RCC with Sunitinib Resistance (lncARSR) is a novel lncRNA that functions as a potential biomarker and is involved in the progression of cancers. However, the clinical significance and molecular mechanism of lncARSR in bladder cancer (Bca) remains unknow. In this study, we discovered that lncARSR was significantly up-regulated in bladder cancer. In addition, increased expression of lncARSR was positively correlated with higher histological grade and larger tumor size. Further experiments demonstrated that suppression of lncARSR attenuated the proliferation, migration, invasion and epithelial-mesenchymal transition (EMT) process of Bca cells. Mechanistically, lncARSR was mainly located in the cytoplasm and acted as a miRNA sponge to positively modulate the expression of Sex-determining region Y-related high-mobility-group box transcription factor 4 (SOX4) via sponging miR-129-5p and subsequently promoted the proliferation and metastasis of Bca cells, thus playing an oncogenic role in Bca pathogenesis. In conclusion, our study indicated that lncARSR plays a critical regulatory role in Bca cells and lncARSR may serve as a potential diagnostic biomarker and therapeutic target for bladder cancer.	bladder
Seminal Vesicle Tumor Microenvironment.	Primary diseases of the seminal vesicles (SV) are very rare entities.Nonneoplastic lesions of the seminal vesicles include amyloidosis, inflammation, calcification and calculi, radiation-induced changes, and basal cell proliferation.Seminal vesicles are frequently involved by tumors originating elsewhere, in particular by prostatic adenocarcinoma, urothelial carcinoma, and rectal adenocarcinoma. On the contrary, primary tumors of the seminal vesicles are rare. Among these, the most common is seminal vesicle adenocarcinoma. To date, less than 100 cases have been reported in literature. Morphologically, primary SV adenocarcinoma is described as a papillary or sheetlike growth architecture, with trabecular and glandular patterns, composed by hobnail tumor cells, frequently with mucinous differentiation. On the contrary, mesenchymal tumors include benign lesions such as leiomyoma, schwannoma, fibroma, paraganglioma, solitary fibrous tumor, cystadenoma, and mixed epithelial and stromal tumors (MEST).Cystadenoma is a rare benign tumor, while MESTs are biphasic tumors with stromal and benign epithelial components. Histological features such as stromal atypia, mitotic activity, nuclear pleomorphism, and tumor necrosis distinct MEST in low-, intermediate-, and high-grade tumors.In recent years, multiple studies reported a link between tumorigenesis and tumor microenvironment. In this regard, the molecular mechanisms connecting prostate cancer (PCa) progression and the host microenvironment have been described and include extracellular matrix (ECM), myofibroblasts, cancer-associated fibroblasts (CAFs), neuroendocrine cells, adipose tissue, and the immune-modulatory cells. Of note, only one study evaluated the influence of seminal vesicle's tumor microenvironment (SVME) on prostate cancer cells so far. Besides, in vivo experiments in NOD/SCID mice clarified the influence of SVME on PCa progression. As such, the injection of PC3 cells into the prostate or the SV resulted in different tumor aggressiveness, and the incidence of retroperitoneal lymph node metastases was significantly higher in mice models receiving SV injection. These findings demonstrated that SVs (rather than the prostate) offer a stimulating tumor microenvironment for growth and invasion of prostate cancer cells.	bladder
[RENAL CELL CARCINOMA METASTASIS TO BLADDER DURING MOLECULAR TARGETED THERAPY WITH PAZOPANIB: REPORT OF TWO CASES].	Renal cell carcinoma (RCC) metastasis to the bladder is rare. We report two cases that occurred metachronously during pazopanib treatment for other metastases. To our knowledge, this is the first report to demonstrate bladder metastasis from RCC during molecular targeted therapy with pazopanib. (Case 1) A woman in her 60s was referred to our department for evaluation of an incidental right renal tumor. Dynamic CT showed a 6 cm renal cell carcinoma. In February 201X she underwent laparoscopic right radical nephrectomy, revealing clear cell carcinoma (grade 1>2), stage pT3aN0M0. In February 201X+1 she complained of left pelvic pain. She was found to have metastasis to two iliac bones and an occipital bone. She received pazopanib, in addition to a bone modifying agent and radiotherapy for the iliac bones. After 8 months, she complained of asymptomatic gross hematuria in spite of having stable disease for bone metastasis. Cystoscopy showed a 1 cm solitary sessile nonpapillary tumor on the posterior wall. She underwent transurethral resection of bladder tumor (TUR-BT). Histological examination showed metastatic RCC. Thereafter she received sequential therapies (axitinib, sunitinib, nivolumab). She remains alive without recurrence in the bladder 51 months after TUR-BT. (Case 2) A woman in her 60s presented to our department with a complaint of painless gross hematuria. A dynamic CT showed an 8.5 cm renal cell carcinoma and multiple lung metastases. In March 201Y she underwent right radical nephrectomy, revealing clear cell carcinoma (grade 2>3), stage pT2aN0M1. In June 201Y she started pazopanib. After 9 months CT showed a bladder tumor in addition to progression of lung metastases. Cystoscopy showed a 1 cm solitary sessile nonpapillary tumor at dome. She underwent TUR-BT. Histological examination showed metastatic RCC. She had no recurrence in the bladder during follow-up although she died of RCC.	bladder
A Multifunction Lipid-Based CRISPR-Cas13a Genetic Circuit Delivery System for Bladder Cancer Gene Therapy.	The treatment of bladder cancer has recently shown minimal progress. Gene therapy mediated by CRISPR provides a new option for bladder cancer treatment. In this study, we developed a versatile liposome system to deliver the CRISPR-Cas13a gene circuits into bladder cancer cells. After in vitro studies and intravesical perfusion studies in mice, this system showed five advantages: (1) CRISPR-Cas13a, a transcriptional targeting and cleavage tool for gene expression editing, did not affect the stability of the cell genome; (2) the prepared liposome systems were targeted to hVEGFR2, which is always highly expressed in bladder cancer cells; (3) the CRISPR-Cas13a sequence was driven by an artificial tumor specific promoter to achieve further targeting; (4) a near-infrared photosensitizer released using near-infrared light was introduced to control the delivery system; and (5) the plasmids were constructed with three crRNA tandem sequences to achieve multiple targeting and wider therapeutic results. This tumor cell targeting lipid delivery system with near-infrared laser-controlled ability provided a versatile strategy for CRISPR-Cas13a based gene therapy of bladder cancer.	bladder
Involvement of FGFR4 Gene Variants on the Clinicopathological Severity in Urothelial Cell Carcinoma.	Fibroblast growth factor receptor 4 (FGFR4) plays a prominent role in cell proliferation and cancer progression. This study explored the effect of FGFR4 single-nucleotide polymorphisms (SNPs) on the clinicopathological characteristics of urothelial cell carcinoma (UCC). This study was conducted to survey the possible correlation of the polymorphism of FGFR4 to the risk and clinicopathologic characteristics of UCC. Four loci of FGFR4 (rs2011077 T > C, rs351855 G > A, rs7708357 G>A, and rs1966265 A > G) were genotyped via the TaqMan allelic discrimination approach in 428 UCC cases and 856 controls. The results indicated that UCC subjects who carried the SNP rs2011077 TC+CC genotypes were significantly related to a higher tumor stage (odds ratio (OR): 1.751, 95% confidence interval (CI): 1.078-2.846), primary tumor size (OR: 1.637, 95% CI: 1.006-2.662), and histopathologic grading (OR: 1.919, 95% CI: 1.049-3.511). Moreover, the SNP rs1966265 AG+GG genotypes were prominently related to a higher tumor stage (OR: 1.769, 95% CI: 1.082-2.891), primary tumor size (OR: 1.654, 95% CI: 1.011-2.706), and histopathologic grading (OR: 2.006, 95% CI: 1.096-3.674) compared to individuals with AA homozygotes. In conclusion, our data reveal association of FGFR4 polymorphisms with UCC clinicopathologic characteristics. FGFR4 polymorphisms may serve as a marker or therapeutic target in UCC development.	bladder
Insulinoma-associated Protein 1 (INSM1) Expression in Small Cell Neuroendocrine Carcinoma of the Urinary Tract.	Clinical guidelines state that neoadjuvant chemotherapy should be administered before surgery in muscle invasive urinary bladder small cell neuroendocrine carcinoma. Recently described marker insulinoma-associated protein 1 (INSM1) has been reported to be sensitive and specific for neuroendocrine differentiation, however, its efficacy in urinary tract small cell carcinoma is not well established. This study examines immunohistochemical expression of INSM1 on whole tissue sections of urinary tract small cell neuroendocrine carcinoma and compares INSM1 expression with established neuroendocrine markers. Immunohistochemical stains for CD56, INSM1, synaptophysin, and chromogranin were performed on 32 cases of small cell neuroendocrine carcinoma of the bladder. Staining was scored for intensity (0: no staining; 1: weak; 2: moderate; 3: strong) and proportion of cells stained (0: 0%; 1: >0% to ≤25%; 2: >25% to ≤50%; 3: >50% to ≤75%; 4: >75% to 100%). INSM1 was positive (intensity 1 to 3 or proportion 1 to 4) in 87% (28/32) of cases (20 with intensity 2 to 3, 17 with proportion 3 to 4). CD56, synaptophysin, and chromogranin were positive in 75% (24/32), 60% (19/32), and 44% (14/32) of cases, respectively. INSM1 was negative (n=4) or only showed weak intensity staining (n=7) in 34% (11/32) of cases. INSM1 is a sensitive marker of small cell neuroendocrine differentiation of the urinary tract. However, this study suggests that optimal utilization of INSM1 would be inclusion in a limited panel of stains rather than as a stand-alone screening marker given that it is negative or only shows weak intensity staining in a significant proportion of cases.	bladder
BSA-bounded p-cresyl sulfate potentiates the malignancy of bladder carcinoma by triggering cell migration and EMT through the ROS/Src/FAK signaling pathway.	Para-cresyl sulfate (P-CS), a major uremic toxin derived from the metabolites of tyrosine and phenylalanine through liver, existed in the blood of patients with chronic kidney disease (CKD). CKD increases the malignancy in bladder cancers; however, effects of P-CS on bladder cancers are not fully understood. P-CS is conjugated with BSA physiologically, and this study aims to investigate the effects and possible underlying mechanisms of BSA-bounded P-CS on human bladder cancer cells. With P-CS treatment, the intracellular ROS increased in bladder cancer cells. ROS then triggered epithelial-mesenchymal transition (EMT), stress fiber redistribution, and cell migration. With specific inhibitors, the key signals regulating P-CS-treated migration are Src and FAK. This study provided a clinical clue that patients with higher serum P-CS have a higher risk of malignant urothelial carcinomas, and a regulatory pathway of how P-CS regulates bladder cancer migration.	bladder
Exosomal miR-663b targets Ets2-repressor factor to promote proliferation and the epithelial-mesenchymal transition of bladder cancer cells.	Exosomes circulating in biological fluids have the potential to be utilized as cancer biomarkers and are associated with cancer progression and metastasis. MicroRNA (miR)-663b has been found to be elevated in plasma from patients with bladder cancer (BC). However, the functional role of exosomal miR-663b in BC processes remains unknown. Here, we isolated exosomes from plasma and found that the miR-663b level was elevated in exosomes from plasma of patients with BC compared with healthy controls. Exosomal miR-663b from BC cells promoted cell proliferation and epithelial-mesenchymal transition. Moreover, exosomal miR-663b targeted Ets2-repressor factor and acted as a tumor promoter in BC cells. Taken together, our findings suggested that exosomal miR-663b is a promising potential biomarker and target for clinical detection and therapy in BC.	bladder
Do not Forget Burkitt´s Lymphoma! Unusual Case of Primary Malignant Lymphoma of the Prostate in a Young Patient.	Primary Burkitt´s lymphoma (BL) of the prostate is rare in the adolescent population. The etiology remains poorly understood. There has been some proposed associations to Epstein-Barr virus and HIV. Clinical and histopathologic data of a 17-year-old patient who underwent transurethral resection of the prostate was obtained. We report the first case of primary malignant BL of the prostate in a 17-year-old Caucasian male who presented with hematuria, lower urinary tract symptoms. Differential diagnosis of a prostatic mass in adolescent patients must be primary or secondary lymphoma of the prostate, including BL as described for the first time in this article.	bladder
Spotlight on gender-specific disparities in bladder cancer.	Men are at a higher risk of developing bladder cancer, but women present with more advanced disease and have more unfavourable outcomes. Although epidemiologic and genetical studies have underlined the multifactorial aetiology and gender-related differences of bladder cancer, there is lack of evidence-based recommendation for gender-specific management of bladder cancer. We summarize the evidence and most recent findings on gender-specific differences in bladder cancer incidence, diagnosis, treatment and outcome, spotlighting the gender disparities in genetic and hormonal risk factors, pelvic anatomy, diagnostic setting and surgical choices. We reviewed the literature published on PubMed between 1981 and 2018. Males have a threefold to fourfold higher risk of bladder cancer as compared to females; however, women have higher stage-for-stage mortality, being diagnosed with more advanced disease, mostly due to a delay in haematuria evaluation. Numerous studies indicate an increased risk of disease recurrence or progression in women with non-muscle-invasive bladder cancer treated with trans-urethral resection, with or without intravesical chemotherapy or immunotherapy, compared to males. In particular, recent molecular evidence show that there is an excess of female Ta mutant tumours. At the time of radical cystectomy, women have a significantly longer length of hospital stay, operative time, higher blood loss and higher 90-day mortality and perioperative complication rate. Moreover, females are less likely to receive a continent diversion. Future research should guarantee greater inclusion of women in trials and focus on improving the effectiveness of therapies in women, perhaps exploring different therapeutic approaches in men and women. Specific data on functional and oncological outcomes can be analysed to define predictive factors able to guide the surgeon in decisions based on evidence. It is urgently needed to limit gender-related discrepancies in early diagnosis and treatment of bladder cancer. Public awareness and bladder cancer female patients' consciousness on gender inequalities must be similarly uprisen.	bladder
CircRNA circPDSS1 promotes bladder cancer by down-regulating miR-16.	BACKGROUND: Circular RNA (circRNA) circPDSS1 is a recently identified oncogene in gastric cancer, while its roles in other types of cancer are unknown. We investigated the functions of circPDSS1 in urothelial bladder cancer (UBC). MATERIALS AND METHODS: Seventy-two patients (50 males and 22 females, age 38-69 years, mean: 52.3 ± 6.3 years) with UBC were enrolled in Gansu Provincial People's Hospital from August 2015 to August 2018. RT-qPCR was used to measure gene expression levels in both biopsies from UBC patients and in vitro cultivated HT-1197 and UMUC3 cells. Cell transfections were performed to analyze gene interactions. Cell proliferation, transwell migration and invasion assays were performed to analyze the effects of transfections on HT-1197 and UMUC3 cell proliferation, migration and invasion, respectively. RESULTS: We found that circPDSS1 was up-regulated in UBC. Expression levels of circPDSS1 were increased with increase in clinical stages. MiR-16 was down-regulated and correlated with circPDSS1 in UBC. Overexpression of circPDSS1 led to down-regulation of miR-16, while miR-16 overexpression failed to significantly affect circPDSS1. Overexpression of circPDSS1 led to increased proliferation, invasion and migration rates of UBC cells. Overexpression of miR-16 not only led to inhibited proliferation, invasion and migration of UBC cells, but also attenuated the effects of circPDSS1 overexpression. CONCLUSION: Therefore, circRNA circPDSS1 may promote UBC by down-regulating miR-16.	bladder
Comparison of the marginal hazard model and the sub-distribution hazard model for competing risks under an assumed copula.	For the analysis of competing risks data, three different types of hazard functions have been considered in the literature, namely the cause-specific hazard, the sub-distribution hazard, and the marginal hazard function. Accordingly, medical researchers can fit three different types of the Cox model to estimate the effect of covariates on each of the hazard function. While the relationship between the cause-specific hazard and the sub-distribution hazard has been extensively studied, the relationship to the marginal hazard function has not yet been analyzed due to the difficulties related to non-identifiability. In this paper, we adopt an assumed copula model to deal with the model identifiability issue, making it possible to establish a relationship between the sub-distribution hazard and the marginal hazard function. We then compare the two methods of fitting the Cox model to competing risks data. We also extend our comparative analysis to clustered competing risks data that are frequently used in medical studies. To facilitate the numerical comparison, we implement the computing algorithm for marginal Cox regression with clustered competing risks data in the R joint.Cox package and check its performance via simulations. For illustration, we analyze two survival datasets from lung cancer and bladder cancer patients.	bladder